Auris Medical reported disappointing top-line results from a Phase III study of Keyzilen (AM-101) for acute inner ear tinnitus. The TACTT2 trial did not reduce tinnitus loudness and tinnitus burden compared to placebo.
“We are disappointed that our TACTT2 trial did not reach its co-primary efficacy endpoints. The assessment of the trial data is ongoing and we intend to discuss outcomes and our plans for a path forward with regulatory agencies prior to the readout from the TACTT3 trial,” Thomas Meyer, founder, chairman, and CEO, explained.
TACTT2 was studying acute inner ear tinnitus following traumatic cochlear injury or otitis media. The trial was conducted primarily in North America, and 343 patients received either Keyzilen 0.87 mg/mL or placebo. The co-primary endpoints were the improvement in subjective tinnitus loudness from baseline to day 84 and the improvement in tinnitus burden from baseline to day 84.
TACTT3, which is being conducted in Europe, is studying acute and postacute inner ear tinnitus following traumatic cochlear injury or otitis media. The trial has enrolled more than 300 patients during the acute tinnitus stage (Stratum A) and approximately 330 patients during the postacute tinnitus stage (Stratum B). The primary endpoint is the change in tinnitus loudness from baseline to day 84; the change in the tinnitus functional index (TFI) is the key secondary efficacy outcome. Results from TACTT3 are expected later this year.
Keyzilen is a small-molecule N-methyl-D-aspartate (NMDA) receptor. According to the company, evidence suggests that NMDA receptors in the cochlea play a major role in the occurrence of tinnitus following acute injury to the inner ear, e.g., from exposure to excessive noise, infections, disturbances in inner ear blood supply, or the administration of certain ototoxic drugs. Persistent overexpression of NMDA receptors may lead to pathologic excitation of auditory nerve fibers, which in the brain is perceived as tinnitus.